TY - JOUR
T1 - Regulated recovery of pulsatile growth hormone secretion from negative feedback
T2 - A preclinical investigation
AU - Veldhuis, Johannes D.
AU - Bowers, Cyril Y.
PY - 2011/10
Y1 - 2011/10
N2 - Although stimulatory (feedforward) and inhibitory (feedback) dynamics jointly control neurohormone secretion, the factors that supervise feedback restraint are poorly understood. To parse the regulation of growth hormone (GH) escape from negative feedback, 25 healthy men and women were studied eight times each during an experimental GH feedback clamp. The clamp comprised combined bolus infusion of GH or saline and continuous stimulation by saline GH-releasing hormone (GHRH), GHRP-2, or both peptides after randomly ordered supplementation with placebo (both sexes) vs. E2 (estrogen; women) and T (testosterone; men). Endpoints were GH pulsatility and entropy (a model-free measure of feedback quenching). Gender determined recovery of pulsatile GH secretion from negative feedback in all four secretagog regimens (0.003 ≤ P≤0.017 for women>men). Peptidyl secretagog controlled the mass, number, and duration of feedbackinhibited GH secretory bursts (each, P < 0.001). E 2/T administration potentiated both pulsatile (P=0.006) and entropic (P=0.001) modes of GH recovery. IGF-I positively predicted the escape of GH secretory burst number and mode (P=0.022), whereas body mass index negatively forecast GH secretory burst number and mass (P =0.005). The composite of gender, body mass index, E 2, IGF-I, and peptidyl secretagog strongly regulates the escape of pulsatile and entropic GH secretion from autonegative feedback. The ensemble factors identified in this preclinical investigation enlarge the dynamic model of GH control in humans.
AB - Although stimulatory (feedforward) and inhibitory (feedback) dynamics jointly control neurohormone secretion, the factors that supervise feedback restraint are poorly understood. To parse the regulation of growth hormone (GH) escape from negative feedback, 25 healthy men and women were studied eight times each during an experimental GH feedback clamp. The clamp comprised combined bolus infusion of GH or saline and continuous stimulation by saline GH-releasing hormone (GHRH), GHRP-2, or both peptides after randomly ordered supplementation with placebo (both sexes) vs. E2 (estrogen; women) and T (testosterone; men). Endpoints were GH pulsatility and entropy (a model-free measure of feedback quenching). Gender determined recovery of pulsatile GH secretion from negative feedback in all four secretagog regimens (0.003 ≤ P≤0.017 for women>men). Peptidyl secretagog controlled the mass, number, and duration of feedbackinhibited GH secretory bursts (each, P < 0.001). E 2/T administration potentiated both pulsatile (P=0.006) and entropic (P=0.001) modes of GH recovery. IGF-I positively predicted the escape of GH secretory burst number and mode (P=0.022), whereas body mass index negatively forecast GH secretory burst number and mass (P =0.005). The composite of gender, body mass index, E 2, IGF-I, and peptidyl secretagog strongly regulates the escape of pulsatile and entropic GH secretion from autonegative feedback. The ensemble factors identified in this preclinical investigation enlarge the dynamic model of GH control in humans.
KW - GHRH
KW - Ghrelin
KW - Human
KW - Pulsatility
KW - Sex steroid
KW - Somatotropin
KW - Testosterone
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U2 - 10.1152/ajpregu.00293.2011
DO - 10.1152/ajpregu.00293.2011
M3 - Article
C2 - 21795635
AN - SCOPUS:80053622852
SN - 0363-6119
VL - 301
SP - R1143-R1152
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 4
ER -